Abstract

Background: Plasmodium vivax is the key obstacle to malaria elimination in Asia and Latin America, largely attributed to its ability to form resilient hypnozoites (sleeper-cells) in the host liver that escape treatment and cause relapsing infections. The decision to form hypnozoite is made early in the liver infection and may already be set in sporozoites prior to invasion. To better understand these early stages of infection, and the potential mechanisms through which the development may be pre-programmed, we undertook a comprehensive transcriptomic, proteomic and histone epigenetic characterization of P. vivax sporozoites. Results: Our study highlights the loading of the salivary-gland sporozoite with proteins required for cell traversal and invasion and transcripts for infection of and development within hepatocytes. We characterise histone epigenetic modifications in the P. vivax sporozoite and explore their role in regulating transcription. This work shows a close correlation between H3K9ac marks and transcriptional activity, with H3K4me3 and H3K9me3 appearing to act as general markers of euchromatin and heterochromatin respectively. We also identify the remarkable transcriptional silence in the (sub)telomeres and discuss potential roles of AP2 transcription factors, specifically ApiAP2-SP and L in regulating this stage. Conclusions: Collectively, these data indicate the sporozoite as a tightly programmed stage primed to infect the human host and identifies key targets to be further explored in liver stage models.

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